The overall objectives of the Virology Core are to elucidate the role of HIV-1 in the development of central nervous system (CNS) impairment, to identify HIV-specific determinants predictive of CNS dysfunction, and to determine the importance of viruses other than HIV-1 on the development of HIV-related CNS disease. In these overall objectives data derived from the Virology Core's longitudinal examination of CSF will be coordinated with studies of neurotropic variants from brain performed by Dr. Wong-Staal's Project, and related studies by the Neuropathology Core. Additionally, cerebrospinal fluid, peripheral blood mononuclear cells and plasma specimens, viral isolates, and nucleic acids (including PCR amplified products) are stored by the Virology Core and are available to other investigators for further virologic investigations. The specific aims of the Virology Core are: (1) To identify virologic markers which are predictive of HIV related CNS disease. We hypothesize that CSF infectious virus load, total DNA, RNA and spliced mRNAs, specific viral phenotypes, and zidovudine resistance will be correlates of CNS impairment. Methods used will include: the quantitation of infectious virus load, quantitation by PCR of viral DNA, RNA, and spliced mRNAs, the determination of viral phenotypes, and assaying for antiretroviral resistance; (2) To identify genotypic properties of HIV-1 within CSF which correlate with neurocognitive dysfunction. We hypothesize that specific HIV-1 genotypes will be associated with the development and presence of CNS impairment. The presence of gp120 genotypes, which correlate with viral phenotypes will be evaluated using PCR amplified sequences of gp120 inserted into a HIV-1 act as cofactors on the development of HIV-related CNS disease. We hypothesize that as HIV-infected persons survive for prolonged periods with low CD4= lymphocyte counts that viruses other than HIV-1 including human cytomegalovirus (as part of the CMV Project), herpes simplex virus types 1 and 2, varicella zoster virus, human herpes virus type 6, Epstein-Barr virus, and JC virus, will become increasing important copathogens contributing to the development of neurocognitive impairment. The findings of the Virology Core will improve the understanding of HIV-1 pathogenesis and enable the design of treatment studies directed toward the prevention of CNS dysfunction in persons identified to be at highest risk for developing abnormalities.